Andy Johnson has been ruled out of England's friendly against Germany at Wembley on Wednesday.
The Everton striker has fluid on his knee and will return to Merseyside for treatment with his club.
Steve McClaren will be unable to call on Liverpool captain Steven Gerrard, Owen Hargreaves, Sol Campbell and Darren Bent after his 28-man squad was depleted by injuries.
The England coach already had a couple of selection headaches to overcome ahead of the Euro 2008 qualifiers against Israel and Russia next month, which striker Wayne Rooney will miss because of his fractured left foot while Peter Crouch must serve a one-match ban.
And McClaren said: "It's an important game in terms of preparation, we have the qualifiers in three weeks which are really big games we need to win.
"This is pure preparation but we're taking it seriously. We're looking forward to the game.
"It has been normal preparation for an England friendly.
"The players had three Premier League games last week, this will be their fourth in 10 days. You get knocks and niggles and we got that. We had to liaise with the clubs and medical staff.
"It's not been ideal but ask any international manager, no preparation is ideal. I know the Germans have got injuries."
McClaren admitted the result is secondary.
"We've got a big game and we've got to make sure we get a performance," he said.
"People talk about injuries but whoever plays will have a great opportunity to play at Wembley, against Germany, in front of a full house. Everyone knows it is a special occasion and that's what we want to make it."